Three areas of investigation will be pursued concurrently. The first involves human helper cell function. Human lymphocytes from individuals naturally sensitized to tuberculin, protein or fungal antigens will be used as carrier protein to determine if human cells exposed to haptenated carriers will produce helper factors capable of helping mouse spleen cells produce anti-hapten antibodies. Similarly, normal human lymphocytes will be exposed to carrier proteins in vitro to sensitize them for this role and they will be compared to cells from individuals sensitized in vivo. The second project involves a desensitization model in which mice immunized with a defined protein antigen are recipients of a cell transfer from syngeneic mice immunized with a heterologous antigenic specificity. The recipient mice are then desensitized to the donor specificity and tested for their residual reactivity to their own (recipient) specificity. This experimental design permits the transferred or donor cells to be manipulated in vitro to determine the nature of these cells and their products. The present proposal will look at the products of the transferred cells and the donor specific antigen to determine how those products suppress the recipient from expressing delayed reactions to the recipient specificity when challenged. The third component involved the elucidation of the mechanism of cutaneous basophil hypersensitivity. Experiments are planned to investigate the suppressive effect of classic DTH (delayed type hypersensitivity) upon the expression of cutaneous basophil hypersensitivity. To do this cells and supernates of DTH reactions will be used in vivo at the site of elicitation of CBH reactions to determine if suppressor substances are present. In addition, animals and people who are anergic to conventional DTH reactions will be tested to determine if they are similarly unresponsive to CBH reactions.